AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

Inclusion Criteria:

• Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

• Peripheral blood blasts > 1%

• Peripheral white blood cell count > 1,000/µl.

• Age ≥ 18 years

• Anticipated treatment with any of the following regimens (Cohort 0) or:

• Cohort 1: A standard induction protocol with infusional cytarabine

• Cohort 2: Decitabine (either 5-day or 10-day regimens)

• Cohort 3: Azacitidine (either intravenous or subcutaneous administration)

• Cohort 4: Decitabine (either 5-day or 10-day) + venetoclax

• Cohort 5: Azacitidine (either intravenous or subcutaneous administration on 7day or 5+2+2 schedule) + venetoclax

• Patients may receive these therapies as part of other on-going clinical trials or asstandard of care treatment.

• Patients in Cohort 1 may receive SOC midostaurin or gemtuzumab ozogamicin, providedthese start after the Day 2 sample is collected. Patients in Cohort 1 may receive astandard combination of cytarabine/idarubicin, cytarabine/daunorubicin, or Vyxeos, aliposomal formulation of cytarabine and daunorubicin.

• ECOG performance status ≤ 3

• Ability to understand and willingness to sign an IRB approved written informedconsent document.

Exclusion Criteria:

• Pregnant or currently nursing

• Prior chemotherapy with hypomethylating agents

• Known history of positive HIV serology.

• Known positive Hepatitis C serology.

• Patient must not have received any chemotherapy within 7 days of enrollment, and anyacute treatment-related toxicities must have returned to baseline. Patients may havereceived hydrea as long as they fulfill peripheral blood blast and peripheral WBCinclusion criteria. Prior TKI therapy is allowed, but must be discontinued within 3days of baseline blood collection.

• Currently receiving any other investigational agents.